Researchers win $3 million grant to develop prenatal test

For families expecting a child, prenatal testing can help parents identify genetic abnormalities in the fetus before the mother enters labour.

But the current “gold standard” prenatal tests, said PhD student Julian Lamanna of the Wheeler Lab, are burdened with a “small but significant risk to both the mother and the baby.”

Amniocentesis, one of the two tests, is associated with miscarriage in about 0.1 to 0.3 per cent of cases, while the other, chorionic villus sampling, risks miscarriage in about 0.2 per cent of cases.

These serious risks of prenatal screening may be avoided in the future, if the research of the Wheeler Lab succeeds in developing its alternative testing procedure.

On February 4, the lab earned a $3 million grant to continue its development of an alternative non-invasive prenatal test from Genome Canada, a non-profit funding agency supported by the federal government.

How does the Wheeler Lab’s prenatal test work?

The test is similar to a “pap smear” used to screen for cervical cancer, explains Lamanna. In a pap smear, a practitioner scrapes away cells from a woman’s cervix, a part of the uterus that widens during childbirth for the passage of a baby, to test for cervical cancer.

In the Wheeler test, a practitioner would similarly use a “soft, bristly brush” to swab the cervix of a pregnant mother. The collected sample would be a “mixture of cervical mucus, as well as a small percentage of cells from the fetus, as well as a large number of cells from the mother.”

The challenge of analyzing the sample is a “needle-in-a-haystack” problem, explains Lamanna. Visualizing a “sticky mixture of mucus that’s very difficult to work with,” clinicians may have to isolate a single cell from the fetus from the one to two thousand sourced from the mother.

“So we need to use a method to differentiate between the two cell types, and then try to use a method to collect only that cell from the fetus,” said Lamanna. “But I think we have a good method of doing so.”

The method to isolate the fetal cells in the sample uses various antibodies – or molecular tags that act as biomarkers – to highlight their cells of interest. The researchers then use a platform that applies a laser to lyse — or break down — these individual fetal cells in the diverse cell population.

The researchers then collect the contents of these lysed fetal cells, amplify the genetic material available for testing, and analyze the material for abnormalities with a “downstream genetic test” currently used in hospitals.

Next steps with the Genome Canada grant

The instrumentation to lyse the cells and collect their contents is unique to the Wheeler lab, and results from phase one funding for the prenatal test project. The phase-two funding from the Genome Canada grant will enable the researchers to scale up the number of samples it can use for analysis, to further compare its method to current methods.

The grant will also enable the team to develop its platform to become more user-friendly for clinicians, which could enable it to be used in hospitals in Toronto, and even throughout Canada.

Doing so will also help keep the costs of the test low, and could even be comparable to the price of current prenatal tests.

The Wheeler Lab’s main goal is to develop “user-friendly instruments that can leave the research lab,” said Lamanna.

Team effort led to project’s success

Lamanna attributed the project’s success to his motivated colleagues, from a wide range of fields.

As Lamanna worked on the biological side to isolate cells in samples, other lab members worked with “different chemicals and assays… to answer a lot of different biological problems.”

Some team members worked on designing the hardware and instrumentation to isolate the cells and isolate their contents, while others worked on the software.

On the clinical side, the Wheeler lab also collaborated with Dr. Elena Kolomietz and Dr. David Chitayat from Mount Sinai Hospital, who collected cell samples for analysis.

“There’s a big team of people that work on this project,” said Lamanna. “I think everyone who works on is super enthusiastic about the potential for the potential positivity of this test, not only in Toronto, but in Canada, and in the rest of the world.”

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Simulating climate change in the lab

New chemistry experiments teach students the effects of greenhouse gases

The role of greenhouse gases in climate change is often misunderstood by the public. Most people know that climate change is caused by increased emissions of greenhouse gases. However, many don’t understand how— for example — carbon dioxide traps heat in the atmosphere.

U of T chemistry professors Jessica D’eon, Jennifer Faust, Kristine Quinlan, and Scott Browning are acutely aware of this knowledge gap and have developed a lab to address it. Their findings were published in the Journal of Chemical Education.

The researchers designed a first-year chemistry laboratory on the greenhouse effect that provides a topical and engaging introduction to the undergraduate student laboratory.

The relatively simple experimental design allows students to focus on grasping complex, big picture concepts without feeling anxious about measurements or dangerous chemicals.

Despite climate science being taught in primary and secondary schools, researchers from Purdue University found that most students enter post-secondary education with a fragmented understanding of the climate system.

D’eon agrees with the findings of this study, writing that many of her students have “put [the mental model] together in a way that is not scientifically sound” and that generally “the greenhouse gas effect has been identified as a poorly understood concept in climate science.”

Now, these tangible experiments are giving students the ‘aha’ moment that they rarely experience when untangling complex and abstract concepts. As students move on from this course to pursue careers in science and non-science disciplines, they will do so with a fundamental understanding of greenhouse gases.

In the first experiment, students are asked to recognize phase changes using dry ice —solid carbon dioxide. Here, they develop a sense of scale while improving their qualitative observation skills.

In the second experiment, students compare types of radiation and energy, discussing their relative importance for the greenhouse effect.

They then apply this knowledge by comparing the heating rates of two ‘beaker Earths’ — one containing a normal atmosphere and another enriched with carbon dioxide. The students observe firsthand the faster rate of warming in the latter beaker, which they can relate back to their studies.

Reflections before and after the experiments indicate that, upon completing this lab, 87 per cent of students significantly improved their mechanistic understanding of the greenhouse effect.

Prior to the experiments, most students gave an unscientific description of greenhouse gases or were too vague in their explanations. After the experiments, students gave more detailed, scientific responses.

Improving students’ fundamental understanding of greenhouse gases contributes to a better-informed future generation of voters who will make critical decisions about how our society tackles climate change.

Natashya Falcone develops healing hydrogel

Natashya Falcone, a PhD candidate working in the Kraatz Research Group at UTSC, is developing substitutes for chemical products that bear financial and environmental costs to produce.

Recently, Falcone developed a hydrogel, a sustainable and economical water-based gel that could repair damaged tissues. The hydrogel is made from amino acids — the building blocks of proteins — and could repair tissues by rebuilding damaged cells.

“We first start off by chemically synthesizing different peptide conjugates by essentially coupling different amino acids together,” explained Falcone in an email toThe Varsity. “We then test the peptide [compound’s] ability to form gels by adding them to various solvents in various conditions to see if they self-assemble into a gel material.”

Though still in testing phases, Falcone hopes the hydrogel will be adapted for use in clinical settings while reducing environmental waste. Falcone will be testing the hydrogel to determine whether it can support cell growth at all. If successful, tests on wounded tissues can begin in vivo.

“We are looking at [using] it for wound healing cell support, for neuronal cell support for different nervous system damage, as well as see how bacteria can interact with these materials,” noted Falcone. “I believe this research can go in many different directions.”

Further development of the substance would also allow for biocompatible and biodegradable tools for tissue engineering and green chemical production. The gels could also be used in academic settings.

In addition, Falcone has developed a cheaper mimic of the NAD coenzyme — a key component in electron transfer reactions — that is already being used in industrial applications.

“This coenzyme is required by a lot of redox enzymes that help drive our metabolism system, as well as enzymes for selective chemical production,” wrote Falcone. “The issue with the natural coenzyme is that it is very expensive and also unstable at the amounts that industries would need if they wanted to use enzymes for large scale chemical production. Synthesizing mimics that are able to replace the natural one would allow a much cheaper, greener and selective chemical production.”

Falcone hopes her research has an impact beyond the laboratory.

“I like the idea of doing the chemistry work and making different materials but then applying them to some biological application to make what I am synthesizing useful and applicable to real life health or environmental problems,” wrote Falcone.

She also reminded budding chemists that responsible stewardship of the Earth should be a priority.

“We are all living on this planet and [it’s] important to take care of it. With everything going on with the pollution, and global warming, and plastics in our ocean,” wrote Falcone. “[It’s] important that we don’t add to destroying our planet with toxic materials.”

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Hold your breath

U of T researchers investigate the effects of nitrous acid on indoor air quality

While conversations surrounding air pollution have largely centred on outdoor pollution, indoor air pollution also poses a threat to public health.

A study led by Douglas Collins, former postdoctoral fellow in the Abatt Group in the U of T Department of Chemistry, explored the effects of nitrous acid on indoor air quality.

In an email interview with The Varsity, Collins, now an Assistant Professor at Bucknell University, identified nitrogen dioxide, ozone, and particulate matter as examples of indoor pollutants.

To simulate nitrous acid chemistry in a realistic environment, Collins and his peers brought lab instruments to an inhabited home and set up experiments to observe the effects of combustion, a known source of nitrous acid and nitrogen oxide.

They compared their measurements to a computational model designed to approximate indoor concentrations of nitrous acid combustion based on a variety of factors.

This is one of the first studies on the effects of nitrous acid composition on indoor environemnts to take place in an inhabited house, as previous studies used lab environments to measure nitrous acid concentrations.

Collins explained that while nitrous acid is one of the lesser known pollutants, it is nevertheless one of the most hazardous. Its reactive nature allows it to act “as a source for other chemically reactive compounds that shape the chemical composition of indoor air.” He added that nitrous acid can also “chemically react with tissues in the respiratory tract and cause adverse health effects.”

Other indoor pollutants include some organic chemicals widely used in plastics, flame retardants, and other common household products.

Indoor air pollution is particularly hazardous to humans because the concentration of air pollutants in enclosed environments can quickly accumulate, and lead to severe health problems like respiratory diseases and cancer.

To make matters worse, many homes now lack sufficient ventilation for air circulation for pollutants to escape, due to new energy-saving regulations.

Other sources of indoor air pollution include asbestos, common in older buildings but universally banned in recent years, tobacco smoke, which clings to clothes and furniture, and chemicals released from space heaters, stoves, and certain cleaning products.

There are several types of indoor air quality meters on the market designed to measure the concentrations of nitrous acid and other air pollutants.

“If you’re interested in monitoring your indoor air, be sure to do your research on which mode is best for your purposes — not all sensors are created equal,” Collins wrote.

Popular air quality sensors include volatile organic compound (VOC) sensors which can pick up organic compounds such as formaldehyde and ketones, carbon dioxide meters, and combined sensors, which can measure a variety of particulate matter, VOCs, and gases. Professional labs are used for exhaustive air quality screening.

A major problem with indoor air pollution is that hazardous pollutants are in nearly all household products and are emitted through common tasks, such as cooking.

However, there are ways to improve air quality, including opening windows to improve ventilation and using ventilation fans in the house.

“The fan above the kitchen stove can be an effective way to remove polluted air from your home, especially when cooking, which is one example of an activity that makes lots of pollutants including HONO [nitrous acid] if you have a gas stove,” Collins wrote. “Refraining from using scented candles or incense is another way to stop pollutants from being introduced to your indoor air. Purchasing a good-quality HEPA air cleaner is also a good idea.”

The National Human Activity Pattern Survey reports Canadians spend almost 90 per cent of their time indoors. It is therefore imperative that we understand the effects of indoor pollution and find ways to improve indoor air quality.

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RealAtoms reinvents the molecular model kit

Founders Ulrich Fekl and Joshua Moscattini aspire to create a new standard for chemistry model kits

RealAtoms is the first reaction modelling kit of its kind. PHOTO COURTESY of ULRICH FEKL

Around this time of year, students purchase molecular model kits from the bookstore. These kits come with parts to create ball-and-stick models, but they are rigid and rather unreflective of the dynamic reactions taught in courses like organic chemistry.

“You have a visual picture of atoms shuffling around, and it’s very hard to communicate it in undergraduate classes,” says Professor Ulrich Fekl of UTM’s Department of Chemical and Physical Sciences.

For instance, in existing model kits, the carbon atom can only form four bonds, and the models are unable to show chemical reactions and intermediates.

As such, teaching reactions and mechanisms becomes difficult for instructors, who could resort to animations and videos, but this approach lacks a tactile experience.

This lack of flexibility is what inspired Fekl and U of T alum Joshua Moscattini to found RealAtoms.

“I always have this mental picture of atoms rearranging and it’s really, really smooth, and there is something enjoyable and memorable about touching models,” says Fekl. But “rearranging and the tactile experience don’t mesh with the existing kits.”

RealAtoms is a dynamic molecular model kit developed with the goal of being able to model and visualize organic and inorganic chemistry reactions, including their intermediates.

The kit comes with 12 hydrogens, six carbons, one nitrogen, and two oxygens. The carbons, nitrogen, and oxygens all have the same composition and can be used interchangeably.

“We call it the molecular reaction kit,” says Fekl.

Fekl developed prototypes of the molecular kit with support from his department, its Chair Claudiu Gradinaru, as well as the Impact Centre.

Moscattini, who is a sessional instructor at U of T and Professor at Seneca College, used his ten years of design experience to help develop RealAtoms using 3D Design.

With RealAtoms there are more possibilities. SN2 reactions can be observed in the hands of the user. The atoms of this kit are capable of showing the entire process from a nucleophilic attack, a five-coordinate carbon representing the intermediate, and finally the exit of the leaving group.

The Walden inversion — the conversion of a molecule from one enantiomer to another — cannot be demonstrated using current model kits, but can be done with RealAtoms with ease.

The kit can also be used for inorganic studies. The atoms in the kit are also able to form transition metal complexes and show square planar and octahedral geometries, and can be used to create lattice structures, and organic and inorganic molecules.

Unlike typical ball-and-stick models, parts in the RealAtoms kit contain magnets enclosed in ABS plastic. According to Fekl, magnetic model kits can already be purchased, but the magnets in the kits don’t contribute to their function.

The magnets used in RealAtoms are functional and allow users to quickly assemble and change a molecule’s geometry.

The model kit also allows users to feel the resistance when rotating bonds.

The model clearly shows that the single bonds of sp3 hybridized carbons can freely rotate, while the double bonds of sp2 hybridized carbons, which cannot rotate.

To form molecules with double or triple bonds, traditional ball-and-stick models would require completely different sticks to form them. The molecule must also be taken apart in order to transition between the different geometries.

However, the atoms in the RealAtoms model kit contain plane surfaces along with concave and convex surfaces. These surfaces, contributed by Moscattini, lock in the orientation of a molecule to prevent rotation around the double bond.

Fekl and Moscattini hope to create a new standard for organic and inorganic model kits.

The model kit became commercially available for the first time at the 2018 Canadian National Exhibition. Moscattini delivered a pitch that won the Kids Technology Pitch Competition. It is also currently being used in a study at Seneca College to investigate the benefits of model kits in chemistry education.

“The overall goal, I think, is for this to be the new standard in terms of organic model kits and inorganic kits,” says Moscattini. “We’re aiming for that, to have it in classrooms across Canada and the rest of North America.”

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Researchers model chemical bonds using quantum computers

The multi-qubit simulation of a quantum chemistry calculation is a world first

A group of researchers including Alán Aspuru-Guzik, U of T professor and Canada 150 Research Chair in Theoretical & Quantum Chemistry, has achieved a world first in quantum chemistry.

A recent study in Physical Review X published the findings of a quantum computer used to calculate the ground-state energy of molecular hydrogen (H2) and lithium hydride (LiH). Ground state refers to the lowest possible energy level of electrons in an atom or molecule.

Although these bonds have been simulated before, this is the first time a multi-qubit — pronounced ‘cue-bit’ — system has been used. While qubits are the basic unit of quantum information, classical computing uses basic units known as bits, which are unable to solve complex computations.

Quantum chemistry is a subfield of chemistry that uses quantum mechanics to model physical systems like chemical bonds and reactions. Quantum chemistry uses ground states, transition states, and excited states to model bonds and reactions.

Where transition states signify the highest possible energy levels in a given molecule or atom, excited states include all energy levels when moving between ground and transition states.

Many advances have been made in the field of quantum chemistry in years prior. In 2010, the hydrogen atom was simulated using photonic and nuclear magnetic resonance experiments.

In 2013, another photonic experiment was used to simulate the hydrohelium cation HeH+. In 2015, the dissociation curve of the same cation was modelled.

We saw the first scalable quantum chemistry simulator on a superconducting platform in 2016, and in 2017, three molecules — H2, LiH, and beryllium hydride, or BeH2, — were simulated on a superconducting qubit platform.

However, these experiments involving ion-trap implementation were limited to a single qubit.

In contrast, this experiment used the trapped-ion model, which was implemented in conjunction with the variational quantum eigensolver (VQE) algorithm. This algorithm was used to calculate the molecular ground-state energies of H2 and LiH, which were then used to simulate their respective bonds.

In effect, the ions are isolated in free space using electromagnetic fields and, once stabilized, they are used to store qubits. This allows quantum information to be transferred through the motion of the ions in a shared trap.

Lasers are used to induce coupling between the internal qubit states and the external motional states for multi-qubit experiments. In other words, the ions become excited and move from a lower energy state to a higher one, which leads to an increase in ion size and allows them to start interacting. The more qubits involved, the more data is shared.

This groundbreaking study is an indication that data processing and collection through quantum computers could become faster, leading to practical applications in many areas from medicine to artificial intelligence.

Currently, even the largest supercomputers are struggling to accurately model molecules. The researchers chose to model H2 and LiH because they are easily understood molecules, and can be modelled using classical computers. Modelling simple bonds helps to pinpoint the accuracy of quantum computing and refine its applications to chemistry.

Simulations of said molecules would allow scientists to model and understand different chemical reactions with lower energy pathways. This would enable the design of new catalysts — substances that increase the rate of reactions — by reducing the amount of energy needed to start them.

The production of new catalysts could lead to the development of new fertilizers, better batteries, and organic solar cells.

The high speed afforded by quantum computing could also benefit the medical field. Masses of data produced through biomedical research on genomes could be more easily shared and handled by scientists. This, in turn, could lead to advances in personalized medicine, useful in treating diseases such as cancer.

More research is still needed to limit errors and their consequences, especially as the VQE method is vulnerable to calibration errors early on, and some errors cannot directly be recovered from.

But with developments in machine learning, scientific discoveries in fields like chemistry can be made much more quickly, and can lead to more advancements.

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The newcomers at the table

Now that the seventh row of the periodic table is complete, what’s next?

A periodic table of the elements in a chemistry classroom at U of T. Tosin Maiyegun/THE VARSITY

On December 30 2015, the scientific community received a late Christmas present from the International Union of Pure and Applied Chemistry (IUPAC): the recognition of four new elements, which completes the periodic table. A joint Russian-American research team is credited for the discovery of elements number 115, 117, and 118, and the discovery of element number 113 is accredited to a Japanese research team.

Though the hardest part of discovering new elements is over, the researchers will have the task of giving suitable names to the elements. TheIUPAC regulations state that elements must be named after “one of their chemical or physical properties, a mythological concept, a mineral, a place or country, or a scientist.” Once everything is commercialized, we can expect the new periodic tables to appear in new chemistry textbooks.

However, according to Robert Batey, the Chair of the U of T chemistry department, the U of T community should not expect to see the periodic tables around the chemistry department change any time soon.

Since the new elements were created synthetically through nuclear reactions using particle colliders, it is unlikely that they will be found naturally on Earth. The instability of the newly discovered elements makes it unlikely that practical uses will emerge from their discovery.

“The amount of element produced is so tiny that it really doesn’t have any practical benefit. It is more of an intellectual development more than anything else,” said Batey.

The completion of the seventh row of the periodic table is certainly a great achievement for the scientific community. The table allows scientists to predict the chemical and physical properties of each element according to their position in the table. It is the first time since 2011 that the table has been updated.

Dmitri Mendeleev was the first to compose a periodic table, in 1869, which characterized elements according to the element’s atomic number.

Now that the seventh row is complete what happens next is the question on everyone’s minds. There certainly has been speculation about the uncharted eighth row. At least until element number 120, all the elements can be arranged according to blocks (s-, p-, d-, and f-) on the periodic table. Batey has suggested that the real excitement would be caused by a discovery beyond element number 120. This would mean creating a whole new g-block for the element, prompting chemists and physicists to redesign the periodic table.

However there is no need to wait in anticipation, as there is no timeline for when scientists will discover g-block elements. Though there have been predictions about elements that are heavy but stable enough to exist for a longer period of time, it may be the case that these elements are too unstable to make. “Maybe this is it,” says Batey, “maybe this is the end, we’ve reached it, the rest can’t be made, but my gut feeling is probably that’s not the case.”

The Japanese Riken Lab expressed the same opinion as they announced that they would continue the pursuit of discovering new elements. Since there is no chemistry for the g-block elements, it would be a redefining moment for the world if chemists and physicists ever reach that region of the periodic table.